How to Define Fast and Slow Progressors in Any-Type Occlusion Acute Ischemic Stroke.

The variable rate of infarct progression in acute ischemic stroke as assessed by various thresholds excludes a substantial proportion of patients due to time or core constraints. We evaluated 106 patients with any-type occlusion to compare these thresholds and assessed performance of hypoperfusion index (HI) for fast and slow rate of infarct progression. Seven (12.5%) were classified fast progressors and 23 (46%), 25 (50%), 12 (24%), and 33 (66%) slow progressors using different core and time criteria. In comparison, HI categorized 100% (n = 106) of cohort with optimal cutoff 0.5 for any-type occlusion (slow progressors: HI ≤ 0.5), sensitivity/specificity 100%/91%, AUC 0.94, and indicative of eligibility for reperfusion and clinical outcomes (median 90-day modified Rankin Scale; 2 for HI ≤ 0.5 versus 5). Estimation of progressors by HI seems comprehensive but needs external validation.

Protecting thermodynamic stability of protein: The basic paradigm against stress and unfolded protein response by osmolytes.

Organic osmolytes are known to play important role in stress protection by stabilizing macromolecules and suppressing harmful effects on functional activity. There is existence of several reports in the literature regarding their effects on structural, functional and thermodynamic aspects of many enzymes and the interaction parameters with proteins have been explored. Osmolytes are compatible with enzyme function and therefore, can be accumulated up to several millimolar concentrations. From the thermodynamic point of view, osmolyte raises mid-point of thermal denaturation (Tm) of proteins while having no significant effect on ΔGD° (free energy change at physiological condition). Unfavorable interaction with the peptide backbone due to preferential hydration is the major driving force for folding of unfolded polypeptide in presence of osmolyte. However, the thermodynamic basis of stress protection and origin of compatibility paradigm has been a debatable issue. In the present manuscript, we attempt to elaborate the origin of stress protection and compatibility paradigm of osmolytes based on the effect on thermodynamic stability of proteins. We also infer that protective effects of osmolytes on ΔGD° (of proteins) could also indicate its potential involvement in unfolded protein response and overall stress biology on macromolecular level.

Association of CT-Based Hypoperfusion Index With Ischemic Core Enlargement in Patients With Medium and Large Vessel Stroke.

BACKGROUND AND OBJECTIVES: The rate of infarct core progression in patients with acute ischemic stroke is variable and affects outcome of reperfusion therapy. We evaluated the hypoperfusion index (HI) to estimate the initial rate of core progression in patients with medium vessel occlusion (MeVO) compared to large vessel occlusion (LVO) stroke and within a larger time frame since stroke onset. METHODS: Core progression was assessed in 106 patients with acute stroke and CT perfusion. Using reperfusion trial core time criteria, fast progressors had core >70 mL within 6 hours of stroke onset and slow progressors had core ≤70 mL, mismatch ≥15 mL, and mismatch to core ratio ≥1.8 within 6 to 24 hours. The relationship between HI and infarct core progression (core/time) was examined using receiver operating characteristics to determine optimal HI cutoff. The HI cutoff was then tested in the overall cohort, compared between MeVO and LVO, and evaluated in patients up to 24 hours from stroke onset to differentiate fast from slow rate of core progression. HI threshold was assessed in a second independent cohort of 110 patients with acute ischemic stroke. RESULTS: In 106 patients with acute stroke, 6.6% were fast progressors, 27.4% were slow progressors, and 66% were not classified as fast or slow progressor by reperfusion trial core time criteria. HI >0.5 was associated with fast progression and able to distinguish fast from slow progressors (area under the curve [AUC] 0.94; 95% confidence interval [CI] 0.80-0.99). In MeVO (n = 26) HI >0.5 had a core progression of 0.30 mL/min compared to 0.03 mL/min for HI ≤0.5 (p < 0.001). In LVO (n = 80), HI >0.5 had a core progression of 0.26 mL/min compared to 0.02 mL/min for HI ≤0.5 (p < 0.001). In patients not classified as fast or slow progressor by reperfusion trial criteria, those with HI >0.5 had progression rate of 0.21 mL/min compared to 0.03 mL/min for those with HI ≤0.5 (p < 0.001). Validation in a second cohort of patients with acute ischemic stroke (n = 110; MeVO = 42, LVO = 68) yielded similar results for HI >0.5 to distinguish fast and slow core progression with an AUC of 0.84 (95% CI 0.72-0.97). DISCUSSION: HI can differentiate fast from slow core progression in MeVO and LVO within the first 24 hours of acute ischemic stroke. Consideration of core progression rate at time of stroke evaluation may have implications in the selection of patients with MeVO and LVO stroke for reperfusion therapy that warrant further study.

Comparison of efficacy of dexamethasone and methylprednisolone in moderate to severe covid 19 disease.

BACKGROUND: The first case of Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were diagnosed in Wuhan, China in 2019. In the first half of 2020 this disease has already converted into a global pandemic. Various treatment options were being tried all over the world. Some studies showed beneficial effects of corticosteroids in covid 19. Hence, we designed this study to compare the effect of two steroids in moderate to severe covid 19 disease. OBJECTIVES: To compare the efficacy and safety of dexamethasone and methylprednisolone in moderate to severe covid 19 disease. STUDY SETTINGS: Fatima Memorial Hospital, Lahore and Ganga Ram hospital, Lahore. STUDY DESIGN: Quasi experimental, interventional study. DURATION OF STUDY: From 1st June 2020 to 30th June 2020. METHODOLOGY: Sample size and technique: there were total 100 patients; 35 patients received dexamethasone and 65 were kept in methylprednisolone receiving group. RESULTS: The mean age of patients was 57.91 years in dexamethasone group and 54.86 years in methylprednisolone group. In dexamethasone group, there were 15 (42.8%) critically ill patients who were shifted to Intensive care unit (ICU) and seven (20%) of them needed ventilatory support, whereas in methylprednisolone group 22 (33.8%) had to be admitted in ICU with eight (12.3%) patient needing ventilator. As outcome measure, patients in both the groups showed marked improvement in temperature, oxygen requirement and C-reactive protein (CRP) on day 5. Only six (17.1%) patient died who received dexamethasone while 10 (15.3%) patients died among those receiving methylprednisolone. CONCLUSION: Dexamethasone and methylprednisolone both are equally effective in treating moderate to severe covid 19 disease.

Left ventricular mass and functions in normotensive offspring of hypertensive parents: an echocardiographic study.

OBJECTIVE: Published observations about cardiovascular alterations in normotensive individuals genetically predisposed to develop essential hypertension are conflicting. We tested the hypothesis that abnormalities in left ventricular mass and/or functions may be present in normotensive children of hypertensive parents. METHODS: One hundred normotensive offsprings (6 to 18 year age) of hypertensive parents (OHP) and an equal number of age- and sex-matched normotensive offsprings of normotensive parents (ONP) were studied with 2-dimensionally guided M-mode and Doppler echocardiography for left ventricular (LV) dimensions, mass, and systolic and diastolic functions. RESULTS: Both the groups had similar body mass index and blood pressure levels. LV dimensions and LV mass in OHP were higher than the corresponding values in ONP but the differences were not statistically significant. LV mass in male OHP was higher than in female OHP; LV mass was also higher when the mother rather than father was hypertensive. None of these differences were statistically significant, however. LV systolic functions were normal and identical in the two subject groups. Indices of LV diastolic function (peak early filling velocity and its deceleration time and late filling velocity) were also normal and similar in the two groups. CONCLUSION: We conclude that children with a family history of essential hypertension have modest alterations in LV mass and these alterations might have a genetic basis separate from but possibly co-inherited with the trait of essential hypertension.

DWI lesion volume reduction following acute stroke treatment with transient partial aortic obstruction.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) identifies acute cerebral ischemia and DWI lesions are thought to indicate irreversibly damaged areas. However, new evidence suggests that DWI lesions may be reversible, especially with reperfusion. We present a patient who showed substantial reversal of her acute DWI lesion following partial aortic occlusion with Neuroflo™, a novel dual balloon catheter (Neuroflo™, CoAxia, MN). METHODS: Case report/literature review. RESULTS: A 48-year-old woman presented with left-sided weakness and demonstrated an acute DWI lesion in the right middle cerebral artery territory, with diffusion-perfusion mismatch. She was enrolled into an experimental study in which a dual balloon catheter was inflated in the lower aorta. The patient improved and her postprocedure magnetic resonance image showed a significant reduction in lesion volume on diffusion and perfusion-weighted imaging. At 1 month, a repeat computed tomography scan showed a small infarction in the right insula, lentiform nucleus, and frontal cortex. The patient had recovered with no significant disability at her 3-month follow-up. CONCLUSION: Reperfusion can improve DWI lesions. Partial aortic obstruction with a novel dual balloon catheter may be useful to promote reperfusion.

Polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is the most common reproductive endocrinopathy of women during their childbearing years. A significant degree of controversy exists regarding the etiology of this syndrome, but there is a growing consensus that the key features include insulin resistance, androgen excess, and abnormal gonadotropin dynamics. Familial and genetic factors cause predisposition to PCOS. Insulin resistance and adiposity put women with PCOS at a higher risk for diabetes, hypertension, dyslipidemia, and cardiovascular disease. Even though the adverse health consequences associated with PCOS are substantial, most women are not aware of these risks. Early recognition and treatment of metabolic sequelae should be the main focus of clinicians. Lifestyle modifications, mainly a balanced diet, weight loss, and regular exercise, are of utmost importance. On the pharmacologic front, various therapies including metformin, thiazolidinediones, and others appear to be very promising in the management of cardiometabolic aspects of PCOS.